Deleted in liver cancer-1 (DLC-1): A tumor suppressor not just for liver
Deleted in liver cancer-1 (DLC-1): A tumor suppressor not just for liver
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DOI：
10.1016/j.biocel.2007.04.008
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发表时间：
2008-01-01
影响因子：
4
通讯作者：
Lo, Su Hao
中科院分区：
文献类型：
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作者：
Liao, Yi-Chun;Lo, Su Hao
DLC-1，顾名思义，最初是作为一种在肝细胞癌中经常缺失的潜在肿瘤抑制基因被分离出来的。进一步的研究表明，通过基因组缺失或DNA甲基化降低DLC-1的表达与多种癌症类型相关，包括肺癌、乳腺癌、前列腺癌、肾癌、结肠癌、子宫癌、卵巢癌和胃癌。DLC-1在癌细胞中重新表达可调节肌动蛋白细胞骨架结构和局灶黏附，显著抑制细胞生长，支持其抑瘤作用。这种肿瘤抑制功能依赖于DLC-1的RhoGTPase激活蛋白（RhoGAP）活性和类固醇急性调节（StAR）相关脂质转移（START）结构域，以及它的局灶粘附定位，这是由张力蛋白的Src同源性2 （SH2）结构域以不依赖磷酸酪氨酸的方式募集的。因此，DLC-1的表达和亚细胞定位可能是癌症预后的一个有用的分子标志物，而DLC-1及其下游信号分子可能是治疗癌症的靶点。(C) 2007 Elsevier Ltd.版权所有。
Deleted in liver cancer 1 (DLC-1), as its name implied, was originally isolated as a potential tumor suppressor gene often deleted in hepatocellular carcinoma. Further studies have indicated that down-expression of DLC-1 either by genomic deletion or DNA methylation is associated with a variety of cancer types including lung, breast, prostate, kidney, colon, uterus, ovary, and stomach. Re-expression of DLC-1 in cancer cells regulates the structure of actin cytoskeleton and focal adhesions and significantly inhibits cell growth, supporting its role as a tumor suppressor. This tumor suppressive function relies on DLC-1's RhoGTPase activating protein (RhoGAP) activity and steroidogenic acute regulatory (StAR)-related lipid transfer (START) domain, as well as its focal adhesion localization, which is recruited by the Src Homology 2 (SH2) domains of tensins in a phosphotyrosine-independent fashion. Therefore, the expression and subcellular localization of DLC-1 could be a useful molecular marker for cancer prognosis, whereas DLC-1 and its downstream signaling molecules might be therapeutic targets for the treatment of cancer. (C) 2007 Elsevier Ltd. All rights reserved.